Telisotuzumab Adizutecan Shows Promise in c-Met-Expressing Solid Tumors
核心洞察
Telisotuzumab adizutecan (ABBV-400) demonstrates antitumor activity in non-small cell lung cancer (NSCLC (搜索)) and gastroesophageal cancer (GEA (搜索)) patients in a Phase 1 study.
In EGFR (搜索) wild-type NSCLC (搜索), ABBV-400 achieved a 43.8% objective response rate (ORR) and an 85.4% clinical benefit rate at 2.4/3.0 mg/kg every three weeks.
GEA (搜索) patients treated with ABBV-400 at 3.0 mg/kg every three weeks showed a 28.6% ORR and a 71.4% clinical benefit rate.
AbbVie (搜索)'s telisotuzumab adizutecan (ABBV-400), an antibody-drug conjugate (ADC) targeting c-Met (搜索), is showing promising early results in patients with advanced solid tumors, particularly non-small cell lung cancer (NSCLC (搜索)), gastroesophageal cancer (GEA (搜索)), and colorectal cancer (CRC (搜索)). Data from a Phase 1 study (NCT05029882) presented at the 2024 ESMO Congress and other meetings highlight the potential of this next-generation ADC in addressing unmet needs in these tumor types.
Activity in Non-Small Cell Lung Cancer
In a Phase 1 study, ABBV-400 was evaluated in patients with advanced EGFR (搜索) wild-type non-squamous NSCLC (搜索). Preliminary data showed that among 48 previously treated patients, ABBV-400, when dosed at 2.4 and 3.0 mg/kg every three weeks, achieved a confirmed objective response rate (ORR) of 43.8% and a clinical benefit rate of 85.4%. These results suggest that ABBV-400 has the potential to provide meaningful clinical benefit in this patient population.
Gastroesophageal Cancer Findings
Preliminary data from the same Phase 1 study also demonstrated antitumor activity in GEA (搜索) patients. Among 42 patients treated with ABBV-400 at a dose of 3.0 mg/kg every three weeks, the confirmed ORR was 28.6%, and the clinical benefit rate was 71.4%. These findings indicate that ABBV-400 may offer a new treatment option for patients with advanced GEA.
Colorectal Cancer Insights
Telisotuzumab adizutecan also demonstrated early signals of antitumor activity in colorectal cancer (CRC (搜索)). In heavily pretreated patients with metastatic CRC with c-Met (搜索) expression of 10% or more by 3+ immunohistochemistry staining intensity, the overall response rate was 37.5% at the telisotuzumab adizutecan dose level of 2.4 mg/kg or higher. According to Dr. Strickler, patients with higher levels of c-Met expression appear to derive even greater benefit.
Mechanism of Action
Telisotuzumab adizutecan comprises the antibody telisotuzumab, which binds and inactivates the MET receptor, linked to a drug conjugate called adizutecan, a topoisomerase I inhibitor. This ADC targets the c-Met (搜索) protein, which is commonly overexpressed in various advanced solid tumors.
Safety and Tolerability
ABBV-400 at 2.4 and 3.0 mg/kg Q3W has a tolerable and manageable safety profile with promising antitumor activity. Long-term tolerability appears improved at 2.4 relative to 3.0mg/kg with higher relative dose intensity and generally lower treatment-emergent adverse events (TEAEs).